Phosphorus deficiency alleviates iron limitation in Synechocystis cyanobacteria through direct PhoB-mediated gene regulation.

Iron and phosphorus are essential nutrients that exist at low concentrations in surface waters and may be co-limiting resources for phytoplankton growth. Here, we show that phosphorus deficiency increases the growth of iron-limited cyanobacteria (Synechocystis sp. PCC 6803) through a PhoB-mediated regulatory network. We find that PhoB, in addition to its well-recognized role in controlling phosphate homeostasis, also regulates key metabolic processes crucial for iron-limited cyanobacteria, including ROS detoxification and iron uptake. Transcript abundances of PhoB-targeted genes are enriched in samples from phosphorus-depleted seawater, and a conserved PhoB-binding site is widely present in the promoters of the target genes, suggesting that the PhoB-mediated regulation may be highly conserved. Our findings provide molecular insights into the responses of cyanobacteria to simultaneous iron/phosphorus nutrient limitation.

[Mechanism of Jiaotai Pills in treatment of depression by UHPLC-TOF-MS combined with network pharmacology and experimental validation].

This study aims to analyze the constituents of Jiaotai Pills migrating to the blood in normal rats by UHPLC-TOF-MS technique and reveal the underlying mechanism of Jiaotai Pills in the treatment of depression by network pharmacology and animal experiments. UHPLC-TOF-MS technique was used to detect the constituents of Jiaotai Pills in the blood of rats after intragastric administration. The intersection target of the constituents and depression was screened by DisGeNET and SwissTargetPrediction database, and the protein-protein interaction(PPI) network was constructed. Key targets were imported into the DAVID platform for Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway annotation. Combined with constituents, targets, and pathways, the "constituent-target-pathway" network was constructed by Cytoscape 3.9.1 software, through which the key targets and pathways of Jiaotai Pills against depression were predicted. The depression model of chronic unpredictable mild stress(CUMS) was established on rats. After that, behavioral experiments were conducted. The expression of inflammatory factors in serum and the neurotransmitters in the brain were detected by ELISA, and the expression of key targets in the hippocampus was detected by Western blot. The results showed that a total of 17 constituents of Jiaotai Pills were identified in the blood, including 10 alkaloids. There were 124 intersection targets between constituents of Jiaotai Pills and depression disorder. A total of 52 core targets were screened according to PPI results, including NLRP3 and caspase-1, etc. KEGG enrichment analysis mainly involved 15 typical pathways such as NOD-like receptor pathway. The results of animal experiments showed that Jiaotai Pills significantly improved the depression-like behavior of CUMS depressive model on rats, decreased the levels of IL-1ß, TNF-α and IL-6 in serum, and increased the expression of neurotransmitters such as 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) in the brain. Besides, Jiaotai Pills also down-regulated the expression of NLRP3 and caspase-1 proteins in the hippocampus and inhibited the NLRP3-mediated NOD-like receptor signaling pathway. In conclusion, Jiaotai Pills may play a role in the treatment of depression by inhibiting the NLRP3 inflammasome and the NOD-like receptor pathway mediated by NLRP3.

Intermittent administration of PTH for the treatment of inflammatory bone loss does not enhance entheseal pathological new bone formation.

OBJECTIVE: To investigate the effect of intermittent parathyroid hormone (iPTH) administration on pathological new bone formation during treatment of ankylosing spondylitis-related osteoporosis. METHODS: Animal models with pathological bone formation caused by hypothetical AS pathogenesis received treatment with iPTH. We determined the effects of iPTH on bone loss and the formation of pathological new bone with micro-computed tomography (micro-CT) and histological examination. In addition, the tamoxifen-inducible conditional knockout mice (CAGGCre-ERTM; PTHflox/flox, PTH-/-) was established to delete PTH and investigate the effect of endogenous PTH on pathological new bone formation. RESULTS: iPTH treatment significantly improved trabecular bone mass in the modified collagen-induced arthritis (m-CIA) model and unbalanced mechanical loading models. Meanwhile, iPTH treatment did not enhance pathological new bone formation in all types of animal models. Endogenous PTH deficiency had no effects on pathological new bone formation in unbalanced mechanical loading models. CONCLUSION: Experimental animal models of AS treated with iPTH show improvement in trabecular bone density, but not entheseal pathological bone formation，indicating it may be a potential treatment for inflammatory bone loss does in AS.

Heat-triggered shape recovery, EMI shielding and flame retardant: A novel cellulose/M(OH)(OCH3)@dopamine@Ag (M=Co, Ni) nanopaper for early fire alarm.

Fire alarm systems are essential for protecting lives and properties from fire hazards. However, most of the existing fire alarm nanopapers rely on the resistance reduction after heating, which requires direct contact with the flame. In this study, we present a novel fire alarm nanopaper (CMPA) based on heat-triggered shape recovery. The CMPA is composed of hydroxypropyl methyl cellulose (HPMC) as the matrix and 2D nanomaterials M(OH)(OCH3) as fillers. When the temperature of CMPA exceeded the glass transition, the thrice-folded CMPA-1.0 flattened in 30s and connected to the alarm circuit based on its conductive surface. According to the results, the CMPA-1.0 with a thickness of about 0.2 mm had an efficient electromagnetic shielding of 42.1 dB. Moreover, the CMPA-1.0 self-extinguished rapidly after being ignited with its original shape preserved. The peak heat release rate of CMPA-1.0 was 108.9 W/g, which was 61.9 % lower than that of HPMC. Furthermore, the thermal conductivity of CMPA-1.0 reached to 0.317 W m-1 K-1, which was 40.8 % higher than that of HPMC, reducing the heat accumulation effectively. This work shows that CMPA is an ideal material for sensitive and safe early fire alarm, and the strategy based on heat-triggered shape recovery is promising in fire alarm application.

Hypothetical chloroplast reading frame 51 encodes a photosystem I assembly factor in cyanobacteria.

Hypothetical chloroplast open reading frames (ycfs) are putative genes in the plastid genomes of photosynthetic eukaryotes. Many ycfs are also conserved in the genomes of cyanobacteria, the presumptive ancestors of present-day chloroplasts. The functions of many ycfs are still unknown. Here, we generated knock-out mutants for ycf51 (sll1702) in the cyanobacterium Synechocystis sp. PCC 6803. The mutants showed reduced photoautotrophic growth due to impaired electron transport between photosystem II (PSII) and PSI. This phenotype results from greatly reduced PSI content in the ycf51 mutant. The ycf51 disruption had little effect on the transcription of genes encoding photosynthetic complex components and the stabilization of the PSI complex. In vitro and in vivo analyses demonstrated that Ycf51 cooperates with PSI assembly factor Ycf3 to mediate PSI assembly. Furthermore, Ycf51 interacts with the PSI subunit PsaC. Together with its specific localization in the thylakoid membrane and the stromal exposure of its hydrophilic region, our data suggest that Ycf51 is involved in PSI complex assembly. Ycf51 is conserved in all sequenced cyanobacteria, including the earliest branching cyanobacteria of the Gloeobacter genus, and is also present in the plastid genomes of glaucophytes. However, Ycf51 has been lost from other photosynthetic eukaryotic lineages. Thus, Ycf51 is a PSI assembly factor that has been functionally replaced during the evolution of oxygenic photosynthetic eukaryotes.

Construction of an infectious cloning system of porcine reproductive and respiratory syndrome virus and identification of glycoprotein 5 as a potential determinant of virulence and pathogenicity.

Porcine reproductive and respiratory syndrome virus (PRRSV) infection of pigs causes a variety of clinical manifestations, depending on the pathogenicity and virulence of the specific strain. Identification and characterization of potential determinant(s) for the pathogenicity and virulence of these strains would be an essential step to precisely design and develop effective anti-PRRSV intervention. In this study, we report the construction of an infectious clone system based on PRRSV vaccine strain SP by homologous recombination technique, and the rescue of a chimeric rSP-HUB2 strain by replacing the GP5 and M protein-coding region from SP strain with the corresponding region from a highly pathogenic strain PRRSV-HUB2. The two recombinant viruses were shown to be genetically stable and share similar growth kinetics, with rSP-HUB2 exhibiting apparent growth and fitness advantages. Compared to in cells infected with PRRSV-rSP, infection of cells with rSP-HUB2 showed significantly more inhibition of the induction of type I interferon (IFN-ß) and interferon stimulator gene 56 (ISG56), and significantly more promotion of the induction of proinflammatory cytokines IL-6, IL-8, ISG15 and ISG20. Further overexpression, deletion and mutagenesis studies demonstrated that amino acid residue F16 in the N-terminal region of the GP5 protein from HUB2 was a determinant for the phenotypic difference between the two recombinant viruses. This study provides evidence that GP5 may function as a potential determinant for the pathogenicity and virulence of highly pathogenic PRRSV.

Infection of sheep by Echinococcus multilocularis in Gansu, China: evidence from mitochondrial and nuclear DNA analysis.

BACKGROUND: In the normal life cycle of the parasite (Echinococcus multilocularis) that causes alveolar echinococcosis, domestic and wild carnivores act as definitive hosts, and rodents act as intermediate hosts. The presented study contributes to the research on the distribution and transmission pattern of E. multilocularis in China having identified sheep as an unusual intermediate host taking part in the domestic transmission of alveolar echinococcosis in Gansu Province, China. METHODS: From 2020 to 2021, nine whitish different cyst-like were collected from the liver of sheep in Gansu Province for examination. A near complete mitochondrial (mt) genome and selected nuclear genes were amplified from the cyst-like lesion for identification. To confirm the status of the specimen, comparative analysis with reference sequences, phylogenetic analysis, and network analysis were performed. RESULTS: The isolates displayed ≥ 98.87% similarity to E. multilocularis NADH dehydrogenase sub-unit 1 (nad1) (894 bp) reference sequences deposited in GenBank. Furthermore, amplification of the nad4 and nad2 genes also confirmed all nine samples as E. multilocularis with > 99.30% similarity. Additionally, three nuclear genes, pepck (1545 bp), elp-exons VII and VIII (566 bp), and elp-exon IX (256 bp), were successfully amplified and sequenced for one of the isolates with 98.42% similarity, confirming the isolates were correctly identified as E. multilocularis. Network analysis also correctly placed the isolates with other E. multilocularis. CONCLUSIONS: As a result of the discovery of E. multilocularis in an unusual intermediate host, which is considered to have the highest zoonotic potential, the result clearly demonstrated the necessity for expanded surveillance in the area.

MSN8C: A Promising Candidate for Antitumor Applications as a Novel Catalytic Inhibitor of Topoisomerase II.

MSN8C, an analog of mansonone E, has been identified as a novel catalytic inhibitor of human DNA topoisomerase II that induces tumor regression and differs from VP-16(etoposide). Treatment with MSN8C showed significant antiproliferative activity against eleven human tumor cell lines in vitro. It was particularly effective against the HL-60/MX2 cell line, which is resistant to Topo II poisons. The resistance factor (RF) of MSN8C for Topo II in HL-60/MX2 versus HL-60 was 1.7, much lower than that of traditional Topo II poisons. Furthermore, in light of its potent antitumor efficacy and low toxicity, as demonstrated in the A549 tumor xenograft model, MSN8C has been identified as a promising candidate for antitumor applications.

Single-Gate In-Transistor Readout of Current Superposition and Collapse Utilizing Quantum Tunneling and Ferroelectric Switching.

In nanostructure assemblies, the superposition of current paths forms microscopic electric circuits, and different circuit networks produce varying results, particularly when utilized as transistor channels for computing applications. However, the intricate nature of assembly networks and the winding paths of commensurate currents hinder standard circuit modeling. Inspired by the quantum collapse of superposition states for information decoding in quantum circuits, the implementation of analogous current path collapse to facilitate the detection of microscopic circuits by modifying their network topology is explored. Here, the superposition and collapse of current paths in gate-all-around polysilicon nanosheet arrays are demonstrated to enrich the computational resources within transistors by engineering the channel length and quantity. Switching the ferroelectric polarization of Hf0.5 Zr0.5 O2 gate dielectric, which drives these transistors out-of-equilibrium, decodes the output polymorphism through circuit topological modifications. Furthermore, a protocol for the single-electron readout of ferroelectric polarization is presented with tailoring the channel coherence. The introduction of lateral path superposition results into intriguing metal-to-insulator transitions due to transient behavior of ferroelectric switching. This ability to adjust the current networks within transistors and their interaction with ferroelectric polarization in polycrystalline nanostructures lays the groundwork for generating diverse current characteristics as potential physical databases for optimization-based computing.

Association between handgrip strength and heart failure in adults aged 45 years and older from NHANES 2011-2014.

Growing evidence indicates that handgrip strength (HGS) is a conspicuous marker for assessing some diseases affecting middle-aged and elderly individuals. However, research regarding HGS and heart failure (HF) is sparse and controversial. Hence, we aimed to investigate the association between HGS and HF among adults aged 45 years and older in the United States. In this cross-sectional study, we included 4524 adults older than 45 years who were part of the National Health and Nutrition Examination Survey. A generalized additive model was used to estimate the association between HGS and HF. Age, gender, race, income, education, body mass index, smoking status, drinking status, diabetes, hypertension, stroke, vigorous physical activity, total energy intake, total protein intake, total sugars intake, and total fat intake covariates were adjusted using multiple regression models. And further subgroup analysis was conducted. We documented 189 cases of HF, including 106 men and 83 women. HGS was negatively associated with HF after adjusting for all the covariates (odds ratio = 0.97, 95% confidence interval = 0.96-0.99; P < 0.001). Compared with the lowest quintile, the highest quintile was associated with an 82% lower incidence of HF (odds ratio = 0.18, 95% confidence interval = 0.08-0.43; P < 0.001). Subgroup analysis showed that the results remained stable. In US adults older than 45, HGS was negatively associated with HF after adjusting for covariates. This finding had the potential to draw attention to the physiological and pathological effects of decreased muscle function on HF and may influence further prospective studies with intervention trials.

[Anti-depression mechanism of Zuojin Pills:based on UHPLC-TOF-MS, network pharmacology, and experimental verification].

This study aims to explore the anti-depression mechanism of Zuojin Pills based on the plasma constituents, network pharmacology, and experimental verification. UHPLC-TOF-MS was used for qualitative analysis of Zuojin Pills-containing serum. Targets of the plasma constituents and the disease were retrieved from PharmMapper and GeneCards. Then the protein-protein interaction(PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.7.2 was employed construct the "compound-target-pathway" network and the targets and signaling pathways of Zuojin Pills against depression were predicted. CUMS-induced depression mouse model was established to verify the key targets. The results showed that a total of 21 constituents migrating to blood of Zuojin Pills were identified, which were mainly alkaloids. A total of 155 common targets of the constituents and the disease and 67 core targets were screened out. KEGG enrichment and PPI network analysis showed that Zuojin Pills may play a role in the treatment of depression through AMPK/SIRT1, NLRP3, insulin and other targets and pathways. Furthermore, the results of animal experiments showed that Zuojin Pills could significantly improve the depression behaviors of depression, reduce the levels of IL-1ß, IL-6 and TNF-α in hippocampus and serum, activate AMPK/SIRT1 signaling, and reduce the protein expression of NLRP3. In conclusion, Zuojin Pills may play a role in the treatment of depression by activating AMPK/SIRT1 signaling pathway, and inhibiting NLRP3 activation and neuroinflammation in the hippocampus of mice.

Pd/MIL-100(Fe) as hydrogen activator for FeIII/FeII cycle: Fenton removal of sulfamethazine.

Masses of iron sludge generated from engineering practice of classic Fenton reaction constraints its further promotion. Accelerating the FeIII/FeII cycle may be conducive to reducing the initial ferrous slat dosage and the final iron sludge. Based on the reduction of Pd/MIL-100(Fe)-activated hydrogen, an improved Fenton system named MHACF-MIL-100(Fe) was developed at ambient temperature and pressure. 97.8% of sulfamethazine, the target pollutant in this work, could be degraded in 5 min under the conditions of 20 mM H2O2, 25 µM ferrous chloride, initial pH 3.0, 2 g·L-1 composite catalyst Pd/MIL-100(Fe) and hydrogen gas 60 mL·min-1. Combining density functional theory (DFT) calculation and intermediate detection, the degradation of this antibiotic was inferred to start from the cleavage of N-S bond. The catalytic of Pd/MIL-100(Fe), demonstrated by the removal efficiency of SMT and the catalyst morphology, remained intact after six reaction cycles. The present study provides an insight into the promotion of Fenton reaction.

Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway.

Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury. However, its effect on spinal cord injury in aged mice remains unclear. Considering the essential role of angiogenesis during the regeneration process, we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells, thereby promoting microvascular regeneration in aged mice after spinal cord injury. In this study, we established young and aged mouse models of contusive spinal cord injury using a modified Allen method. We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord. Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro. Furthermore, intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord, thereby improving neurological function. The role of metformin was reversed by compound C, an adenosine monophosphate-activated protein kinase inhibitor, both in vivo and in vitro, suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury. These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway, thereby improving the neurological function of aged mice after spinal cord injury.

[Mechanism of Jiaotai Pills in treatment of depression based on quantitative proteomics].

This study aimed to investigate the effect of Jiaotai Pills on protein expression in the hippocampus of the rat model of chronic unpredictable mild stress(CUMS)-induced depression by quantitative proteomics and explore the anti-depression mechanism of Jiaotai Pills. The SD rats were randomized into control, model, Jiaotai Pills, and fluoxetine groups(n=8). Other groups except the control group were subjected to CUMS modeling for 4 weeks. After 4 weeks of continuous administration, the changes of behavior and pathological morphology of the hippocampal tissue were observed. Proteins were extracted from the hippocampal tissue, and bioinformatics analysis was performed for the differentially expressed proteins(DEPs) identified by quantitative proteomics. Western blot was employed to verify the key DEPs. The results showed that Jiaotai Pills significantly alleviated the depression behaviors and hippocampal histopathological changes in the rat model of CUMS-induced depression. A total of 5 412 proteins were identified in the hippocampus of rats, including 65 DEPs between the control group and the model group and 35 DEPs between the Jiaotai Pills group and the model group. There were 16 DEPs with the same trend in the Jiaotai Pills group and the control group, which were mainly involved in sphingolipid, AMPK, and dopaminergic synapse signaling pathways. The Western blot results of Ppp2r2b, Cers1, and Ndufv3 in the hippocampus were consistent with the results of proteomics. In conclusion, Jiaotai Pills may play an anti-depression role by modulating the levels of Ppp2r2b, Cers1, Ndufv3 and other proteins and regulating sphingolipid, AMPK, and dopaminergic synapse signaling pathways.

Antimelanogenesis Effect of Methyl Gallate through the Regulation of PI3K/Akt and MEK/ERK in B16F10 Melanoma Cells.

Methyl gallate is a polyphenolic compound found in many plants, and its antioxidant, antitumor, antibacterial, and anti-inflammatory effects have been extensively studied. More recently, antidepressant-like effects of methyl gallate have been demonstrated in some studies. In the present study, we examined the effects of methyl gallate on melanogenesis, including the tyrosinase inhibitory effect, the melanin content, and the molecular signaling pathways involved in this inhibition. The results showed that methyl gallate inhibited tyrosinase activity and significantly downregulated the expressions of melanin synthesis-associated proteins, including microphthalmia-associated transcription factor (MITF), tyrosinase, dopachrome tautomerase (Dct), and tyrosinase-related protein-1 (TRP1). In conclusion, our findings indicated that activation of MEK/ERK and PI3K/Akt promoted by methyl gallate caused downregulation of MITF and triggered its downstream signaling pathway, thereby inhibiting the production of melanin. In summary, methyl gallate showed significant inhibitory activity against melanin formation, implying that it may be a potential ingredient for application in skin-whitening cosmetics.

Coevolution of tandemly repeated hlips and RpaB-like transcriptional factor confers desiccation tolerance to subaerial Nostoc species.

Desert-inhabiting cyanobacteria can tolerate extreme desiccation and quickly revive after rehydration. The regulatory mechanisms that enable their vegetative cells to resurrect upon rehydration are poorly understood. In this study, we identified a single gene family of high light-inducible proteins (Hlips) with dramatic expansion in the Nostoc flagelliforme genome and found an intriguingly special convergence formed through four tandem gene duplication. The emerged four independent hlip genes form a gene cluster (hlips-cluster) and respond to dehydration positively. The gene mutants in N. flagelliforme were successfully generated by using gene-editing technology. Phenotypic analysis showed that the desiccation tolerance of hlips-cluster-deleted mutant decreased significantly due to impaired photosystem II repair, whereas heterologous expression of hlips-cluster from N. flagelliforme enhanced desiccation tolerance in Nostoc sp. PCC 7120. Furthermore, a transcription factor Hrf1 (hlips-cluster repressor factor 1) was identified and shown to coordinately regulate the expression of hlips-cluster and desiccation-induced psbAs. Hrf1 acts as a negative regulator for the adaptation of N. flagelliforme to the harsh desert environment. Phylogenetic analysis revealed that most species in the Nostoc genus possess both tandemly repeated Hlips and Hrf1. Our results suggest convergent evolution of desiccation tolerance through the coevolution of tandem Hlips duplication and Hrf1 in subaerial Nostoc species, providing insights into the mechanism of desiccation tolerance in photosynthetic organisms.

[Pharmacokinetic interaction of Jiaotai Pills and Fluoxetine in rats with CUMS-induced depression].

A high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS) was developed for simultaneously determining the components(magnoflorine, jatrorrhizine, berberrubine, coptisine, berberine) of Jiaotai Pills and Fluoxetine in plasma of rats with chronic unpredictable mild stress(CUMS)-induced depression to investigate the pharmacokinetic herb-drug interaction of Jiaotai Pills and Fluoxetine in the rats. The six components showed good linear relationship within the corresponding concentration ranges, and the method showed high specificity, accuracy, precision, and stability. Their pharmacokinetic parameters were calculated by DAS 3.2.2, and the results showed that the in vivo metabolic processes of the six components accorded with the characteristics of non-compartmental model. When Jiaotai Pills and Fluoxetine were used together, the AUC_(0-t), AUC_(0-∞), C_(max), and C_(av) of magnoflorine all significantly increased(P<0.05), while the pharmacokinetic trend of berberrubine was opposite to that of magnoflorine, as manifested by the decrease in AUC_(0-t), AUC_(0-∞), T_(max), C_(max), and C_(av)(P<0.01, P<0.05). The pharmacokinetic characteristics of jatrorrhizine, coptisine, and berberine followed the trend of berberrubine. There was no significant difference in the pharmacokinetic characteristics of Fluoxetine in the single or combination groups. This study suggests that the enhanced antidepressant efficacy of Jiaotai Pills and Fluo-xetine may be attributed to the pharmacokinetic interaction.

Comparative Effects of Brominated Flame Retardants BDE-209, TBBPA, and HBCD on Neurotoxicity in Mice.

Brominated flame retardants (BFRs) are ubiquitous industrial chemicals. In China, BFRs that are applied in large quantities include decabromodiphenyl ether (BDE-209), tetrabromobisphenol A (TBBPA), and hexabromocyclododecane (HBCD). Although findings are not always unequivocal, mounting evidence in vivo suggests that the BFRs have potential neurotoxicity. The present study aimed to assess and compare the neurotoxic effects of these three BFRs' exposure. Male mice were orally exposed to BDE-209, TBBPA, or HBCD at 50 and 100 mg/kg bw/day for 28 days. The cognitive behavior, oxidative stress (ROS, MDA, and GSH), apoptosis-related genes (caspase-3, bax, and bcl-2), memory-related proteins (BDNF and PSD-95), and neurotransmitters (AChE and ChAT) were detected comparatively. Results showed that high doses of BDE-209, TBBPA, and HBCD exposure impaired spatial memory of mice, elevated ROS and MDA and reduced GSH levels of hippocampus, upregulated caspase-3 and bax expressions, decreased BDNF and PSD-95 levels, and disordered AChE and ChAT levels. Notably, BDE-209 caused greater adverse effects > HBCD > TBBPA. This study confirms and extends that these three BFRs had similar neurotoxic effects at current concentrations, although they may be more or less toxic.

Salidroside ameliorates orthopedic surgery-induced cognitive dysfunction by activating adenosine 5'-monophosphate-activated protein kinase signaling in mice.

Perioperative neurocognitive disorders (PND) are the most common postoperative complications with few therapeutic options. Salidroside, a plant-derived compound, has gained increased attention as a treatment for various neurological diseases and particularly as a modifier of microglia-mediated neuroinflammation. However, the effect of salidroside on orthopedic surgery-induced cognitive dysfunction and the underlying mechanisms are largely unknown. Here, we found that salidroside greatly attenuated cognitive impairment in mice after orthopedic surgery. Neuroinflammation in the mouse hippocampus was also attenuated by salidroside. Meanwhile, salidroside treatment induced a switch in microglial polarization to the anti-inflammatory phenotype. In vitro, salidroside suppressed the expression of proinflammatory cytokines and induced a switch in microglial phenotype to the anti-inflammatory phenotype. Mechanistically, molecular docking studies revealed the potential AMPK activation activity of salidroside. And salidroside did up-regulated the AMPK pathway proteins. Moreover, AMPK antagonist abolished the effects of salidroside in vivo and in vitro. Taken together, our results demonstrated that salidroside effectively suppressed PND by suppressing microglia-mediated neuroinflammation through activating AMPK pathway, and it might be a novel therapeutic approach for PND.

A finite element model of the shoulder: application to the changes of biomechanical environment induced by postoperative malrotation of humeral shaft fracture.

OBJECTIVES: The humerus fracture is one of the most commonly occurring fractures. In this research, we attempted to evaluate and compare the extent of malrotation and biomechanical environment after surgical treatment of humeral shaft fractures. METHODS: A finite element (FE) model of the shoulder was built based on Computed Tomography (CT) data of a patient with a humeral shaft fracture. The muscle group around the shoulder joint was simulated by spring elements. The changes of shoulder stresses under rotation were analyzed. The biomechanics of the normal shoulder and postoperative malrotation of the humeral shaft was analyzed and compared. RESULTS: During rotations, the maximum stress was centered in the posterosuperior part of the glenoid for the normal shoulder. The von Mises shear stresses were 4.40 MPa and 4.89 MPa at 40° of internal and external rotations, respectively. For internal rotation deformity, the shear contact forces were 7-9 times higher for the shoulder internally rotated 40° than for the normal one. For external rotation deformity, the shear contact forces were about 3-5 times higher for the shoulder with 40° external rotation than the normal one. CONCLUSION: Postoperative malrotation of humeral shaft fracture induced the changes of the biomechanical environment of the shoulders. The peak degree of malrotation was correlated with increased stresses of shoulders, which could be paid attention to in humeral shaft fracture treatment. We hoped to provide information about the biomechanical environment of humeral malrotation.